cDNA Sequencing of the 5′ Noncoding Region (5′ NCR) to Determine Hepatitis C Genotypes in Patients with Chronic Hepatitis C

Reports suggest that response tointerferon-alpha therapy is influenced by both hepatitisC viral genotype and titer. Our aim was to determine ifdirect, automated, cycle sequencing of the PCR productfrom an HCV RNA detection assay could be used toreliably determine HCV genotype. In addition, theapproach was used to determine the HCV genotypedistribution in our patient population and to learn ifthere was a correlation between HCV genotype and RNAtiter that could be used to predict response totreatment. In all 143 consecutive patients were testedfor both HCV RNA titer and genotype. Automated, cycle sequencing of PCR product was highly effectiveand failed to yield a genotype in only 3 (2%) patients.The distribution of HCV genotypes was: 1a (40%), 1b(39%), 2a (2%), 2b (6%), 3a (4%). There were significant differences in the median HCV RNA titersbetween genotypes 1, 2, and 3. 6 High HCV RNA titers>4.4 × 10⁶ copies/ml were only seenin genotype 1. However, the HCV RNA level should not beused as a surrogate marker of genotype because of a significantoverlap of titers within the genotypes.     

Outcome after temporal lobectomy in bilateral temporal lobe epilepsy

We determined how noninvasive presurgical data relate to prognosis after temporal lobectomy in patients with independent bilateral temporal lobe (IBTL) complex partial seizures on the intracranial electroencephalogram (EEG). Between 1986 and 1994, 28 patients had IBTL seizures on intracranial EEG. Fifteen of these 28 patients underwent temporal lobectomy and 13 were not offered surgery. Of the 15 patients who had surgery, 10 patients became seizure-free. Magnetic resonance imaging (MRI) and the Wada test were the only variables associated with a seizure-free outcome. Seven of 10 seizure-free patients had a lateralized Wada result or the presence of unilateral hippocampal sclerosis, whereas none of the patients with persistent seizures had either of these findings. Variables not found to be predictive of a seizure-free outcome included location of scalp interictal spikes, degree of seizure-onset laterality, presence of early epilepsy risk factor, duration of epilepsy, and full-scale intelligence quotient. We conclude that MRI and the Wada test provide information of prognostic value in patients with bilateral temporal seizures independent of intracranial EEG data.     

Alzheimer's disease: identical phenotype of familial and non-familial cases

Summary Ninety outpatients with Alzheimer's disease according to ICD-10 diagnostic draft criteria were studied to test the hypothesis that cases with a familial aggregation are different from cases without such an aggregation with respect to cognitive impairment. In all cases the diagnosis of Alzheimer's disease was confirmed by prospective observation within 12 months of initial evaluation. Patients were divided into two groups: one consisting of 23 patients with a familial aggregation, the other consisting of 67 patients without secondary cases among first-degree relatives. By means oft-tests differences in impairment of cognitive functions between the groups were calculated. The results did not yield statistically significant differences between the groups for any of the neuropsychologically investigated cognitive deficits. Thus the hypothesis that the presence of a familial aggregation may lead to a distinct phenotype in Alzheimer's disease was not confirmed.     

Cyclosporine in the treatment of azathioprine-induced red cell aplasia following renal transplantation

Azathioprine, a well-known immunosuppressive agent, is used extensively in renal transplantation. There have been several case reports of pure red cell aplasia induced by this drug following a successful kidney transplant. Previous management of azathioprine-induced red cell aplasia included reduction of azathioprine dose, or treatment with cyclophosphamide. We propose the substitution of cyclosporine for azathioprine, in this clinical setting. Not only does cyclosporine allow recovery of bone marrow function, but it maintains a level of immunosuppression which stabilizes renal function in the post-transplant patient.     

Acetyl-Carnitine and Alzheimer''s Disease

In a double-blind, randomized, controlled clinical trial, progression of Alzheimer's disease was significantly reduced in patients who received acetyl-carnitine (2 g/day) for one year.     

INTRAUTERINE GROWTH RETARDATION

Intrauterine growth retardation (IUGR) occurs in 3% to 10% of all pregnancies. Although it is an uncommon occurrence in a low-risk nurse-midwifery practice, as many as 65% of the cases of IUGR are not identified until after the birth of the infant. Identification of IUGR is important because it carries a high risk of antepartum fetal death, anomalies, intrapartum asphyxia, and long-term morbidity. Additionally, identification of IUGR is essential for appropriate prenatal and intrapartum management. A review of etiologic factors, current assessment, and management of the pregnancy complicated by IUGR is presented, The use and interpretation of new technologies that the clinician may use in diagnosing and managing IUGR is reviewed.     

Detection of the Arg702Trp, Gly908Arg and Leu1007fsinsC polymorphisms of the NOD2/CARD15 gene by real-time PCR with melting curve analysis.

Crohn's disease is a complex disorder, with multiple genetic traits. A frameshift mutation (Leu1007fsinsC) and two missense mutations (Gly908Arg and Arg702Trp) in the NOD2/CARD15 gene are strongly associated with susceptibility to Crohn's disease. The presence of one of these risk alleles confers a 2- to 4-fold increase in the risk of developing Crohn's disease, and the presence of two mutant alleles increases the risk over 20-fold. To facilitate the analysis of these polymorphisms, we developed three LightCycler assays to detect the missense mutations Arg702Trp and Gly908Arg and the frameshift mutation Leu100fsinsC in the NOD2/ CARD15 gene. All three assays can be run simultaneously on one LightCycler using identical cycling parameters. Analysis of 53 DNAs from Crohn's patients helped to identify carriers at allele frequencies similar to other Caucasian populations. The sequencing of such DNAs confirmed the accuracy of the assays. In conclusion, we present three rapid and robust assays to detect the Arg702Trp, the Gly908Arg and the Leu1007fsinsC ins mutations in the NOD2/CARD15 gene [corrected]     

Development of quality of care indicators for Parkinson's disease.

Parkinson's disease (PD) is a major cause of disability. To date, there have been no large-scale efforts to measure the quality of PD care because of a lack of quality indicators for conducting an explicit review of PD care processes. We present a set of quality indicators for PD care. Based on a structured review of the medical literature, 79 potential indicators were drafted. Through a two-round modified Delphi process, an expert panel of seven movement disorders specialists rated each indicator on criteria of validity, feasibility, impact on outcomes, room for improvement, and overall utility. Seventy-one quality indicators met validity and feasibility thresholds. Applying thresholds for impact on outcomes, room for improvement, and overall utility, a subset of 29 indicators was identified, spanning dopaminergic therapy, assessment of functional status, assessment and treatment of depression, coordination of care, and medication use. Multivariable analysis showed that overall utility ratings were driven by validity and impact on outcomes (P < 0.01). An expert panel can reach consensus on a set of highly rated quality indicators for PD care, which can be used to assess quality of PD care and guide the design of quality improvement projects.     

A rare polymorphism affects a mitogen-activated protein kinase site in synapsin III: possible relationship to schizophrenia.

BACKGROUND: Synapsin III plays a role in neuronal plasticity and maps to chromosome 22q12-13, a region suggested to be linked to schizophrenia. To determine if synapsin III plays a role in this disease, we searched for polymorphisms in this gene in patients with schizophrenia and controls. METHODS: The synapsin III gene was initially sequenced from 10 individuals with schizophrenia to identify polymorphisms. Association analysis was then performed using 118 individuals with schizophrenia and 330 population controls. Synapsin III expression was studied by immunoblot analyses, and phosphorylation sites were mapped by sequencing trypsin-digested synapsin III fragments phosphorylated with phosphorus-32. RESULTS: A rare, missense polymorphism, S470N, was identified in the synapsin III gene and appeared more frequently in individuals with schizophrenia than in controls (p =.0048). The site affected by the polymorphism, Ser470, was determined to be a substrate for mitogen-activated protein kinase, a downstream effector of neurotrophin action. Phosphorylation at Ser470 was increased during neonatal development and in response to neurotrophin-3 in cultured hippocampal neurons. CONCLUSIONS: Our observations suggest an association of a rare polymorphism in synapsin III with schizophrenia, but further studies will be required to clarify its role in this disease.